期刊
CELLULAR AND MOLECULAR LIFE SCIENCES
卷 59, 期 3, 页码 478-500出版社
SPRINGER BASEL AG
DOI: 10.1007/s00018-002-8440-8
关键词
platelet; thrombosis; alpha(IIb)beta(3) receptor; glycoprotein IIb/IIIa inhibitor; acute coronary syndrome; myocardial infarction; percutaneous intervention
The central role played by the alpha(IIb)beta(3) receptor in platelet aggregation, and hence in platelet thrombosis, has led to the development of a number of parenteral. and oral glycoprotein (GP) IIb/IIIa inhibitors for use in cardiovascular disease states, such as acute coronary syndromes and stroke. The predominant effect of these agents is to inhibit platelet aggregation, although studies of alpha(IIb)beta(3) receptor function and various GP IIb/IIIa inhibitors have demonstrated the potential for these agents to produce effects on other aspects of platelet function, in addition to non-platelet effects. Overall, clinical studies have demonstrated an impressive beneficial effect for parenteral agents in reducing ischemic complications following percutaneous intervention, and a more modest beneficial effect in the treatment of patients with acute coronary syndromes. Trials with oral GP IIb/IIIa inhibitors in similar patient populations have demonstrated toxicity, manifested by an increased mortality in treated patients. Increased understanding of molecular aspects of both a,,,6, receptor function and the effects of GP IIb/IIIa inhibition may help explain some of the inconsistency in recently reported clinical studies with parenteral agents, and the frank toxicity of oral agents. Such studies may also hold the key to the development of newer agents with enhanced therapeutic benefit.
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